The key point of current biotechnology is the production of heterologous proteins and particularly the production of soluble proteins in native form easily. The production of soluble proteins is important for the synthesis and the recovery of active proteins, the crystallization for functional researches, and the industrialization thereof. Until now many researches related to the production of recombinant heterologous proteins using E. coli. The reason why E. coli is used is that it has many benefits such as easy manipulation, its rapid growth rate, safe expression, low cost and relative convenience of scale-up.
However E. coli has no post-translation chaperons and post-translational processing, thus recombinant heterologous proteins expressed in E. coli are not folded properly or are formed as insoluble inclusion bodies (Baneyx, Curr. Opin. Biotechnol., 10: 411-421, 1999).
In order to solve these problems, researches on the structure and the function of signal sequences based on the fact that signal sequences make proteins be secreted into the periplasm and vectors for expressing soluble heterologous proteins have been developed using various signal sequences from the researches (Ghrayeb et al., EMBO J. 3: 2437-2442, 1984; Kohl et al., Nucleic Acids Res., 18: 1069, 1990; Morika-Fujimoto et al., J. Biol. Chem., 266: 1728-1732, 1991).